RNA Disruption Assay for Early Cancer Survival Prediction
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Solution Overview
Problem
Current methods for predicting survival time in cancer patients, such as complete pathological response (pCR), have limitations, including availability only after therapy and low response rates in ER+ve patients, necessitating an urgent need for an effective intermediate endpoint to assess chemotherapy response before or during treatment.
Innovation Solution
A method involving measuring RNA disruption by determining an RNA disruption assay (RDA) score in tumor tissue samples after cancer treatment, comparing it to reference values, and using the RNA disruption index (RDI) to predict favorable or unfavorable survival prognosis, allowing for early identification of nonresponders and responders to chemotherapy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If complete pathological response (pCR) is used as the endpoint to predict survival, then prediction accuracy is improved, but availability is limited to after therapy completion
Solution Approach 1:
The patent applies preliminary action by measuring RNA disruption in tumor tissue samples during chemotherapy treatment (after 1-3 cycles) rather than waiting for treatment completion. This intermediate measurement provides early prediction of survival outcome, enabling timely treatment adjustments while maintaining prediction accuracy through the use of RNA disruption assay to assess tumor response to chemotherapy
2Reliability
If pCR criteria are used to assess chemotherapy response, then response evaluation is standardized, but response rates are low in ER+ve breast cancer patients
Solution Approach 1:
The patent applies parameter changes by shifting from anatomical response criteria (tumor size reduction) to molecular response criteria (RNA disruption level). The RNA disruption assay measures the extent of RNA fragmentation in tumor cells, providing a sensitive indicator of chemotherapy-induced cell death that correlates with survival benefit, thereby improving both reliability and response rates across different breast cancer subtypes including ER+ve patients
3Ease of operation
If tumor size reduction is used to assess chemotherapy response, then response assessment is simple, but it does not accurately predict survival benefit
Solution Approach 1:
The patent replaces mechanical assessment methods (physical measurement of tumor size by imaging or palpation) with a molecular assay approach. The RNA disruption assay involves extracting RNA from tumor tissue samples and measuring disruption levels through electrophoresis or qPCR, providing a more accurate reflection of cellular response to chemotherapy that directly correlates with survival outcome while maintaining operational feasibility in clinical settings
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This method enables accurate prediction of survival time and response to chemotherapy, allowing for timely adjustments in treatment, such as discontinuing ineffective regimens or switching treatments, thereby improving disease-free and overall survival.
Implementation Method 1
The RDA assay comprises: obtaining at least one electropherogram dataset corresponding to a tumour tissue sample comprising cellular RNA
Data Source
AI summary
A method for the prediction and/or prognosis of survival time of a patient suffering from cancer, comprising the steps of: a) measuring a RDA score in a tumor tissue sample comprising cellular RNA from said patient after said patient has received one or more doses of a cancer treatment; b) comparing said RDA score to one or more predetermined RNA disruption reference values; and c) providing a favorable prediction and/or prognosis of survival time for said patient when said RDA score is higher than said predetermined RNA disruption reference value; or providing an unfavorable prediction and/or prognosis of survival time for said patient when said RDA score is lower than said predetermined RNA disruption reference value, wherein the RDA score is proportional to the degree of RNA disruption.